Counselling following the Prenatal Diagnosis of Klinefelter Syndrome: Comparisons between Geneticists and Obstetricians in Five European Countries

Objective: To describe and compare the information obstetricians and geneticists in five European countries report they would give following the prenatal diagnosis of Klinefelter syndrome. Methods: 388 obstetricians and 269 geneticists from Germany, the Netherlands, Portugal, Spain and the UK completed a brief questionnaire assessing two variables: the information they reported providing to parents following the prenatal diagnosis of Klinefelter syndrome (categorized as positive or negative); and their perceptions of the quality of life with the condition. Results: Geneticists were more likely than obstetricians to report providing more positive than negative information about Klinefelter syndrome than equal amounts of positive and negative information or more negative than positive information about the condition (excess positive information). Regardless of specialty, the information that health professionals reported providing was predicted by their perceptions of the quality of life with the condition, and the country from which they came. Those perceiving quality of life as greater were more likely to provide an excess positive information, as were health professionals from Germany and the UK. Conclusions: These results suggest that the information parents across Europe receive after the prenatal diagnosis of Klinefelter syndrome varies according to the specialty and country of the health professionals consulted, and their perceptions of quality of life with the condition. This variation seems to reflect personal, cultural and professional differences between health professionals. Copyright 2002 S. Karger AG, Basel     

Interaction and structure of surfaces coated by poly(vinyl amines) of different line charge densities

Interactions between preadsorbed films of poly(vinyl amine) (PVA) of two different line charge densities on silica substrates were studied with the colloidal probe technique based on the atomic force microscope (AFM). The preadsorbed films were prepared by adsorption of PVA from a pH 4 solution without any added salt. The highly charged PVA adsorbs in a flat configuration and in laterally heterogeneous layers, while the more weakly charged PVA analog adsorbs in thicker and more homogeneous films. As revealed by reflectivity measurements, such preadsorbed PVA films are stable in polyelectrolyte-free solutions. However, force measurements with the colloidal probe reveal that their interactions depend strongly on the ionic strength. Upon approach, interactions are dominated by electrostatic diffuse layer overlap forces. Both PVA films have very similar diffuse layer charge densities of about 1.5 mC/m2. Since these values are substantially lower than what would be expected from the total charge of the adsorbed polyelectrolytes measured by reflectivity, we infer that coadsorption of anions represents the principal mechanism in charge neutralization. Upon retraction, the adhesion between the films is dominated by bridging forces due to single polymer chains. Such bridging adhesion becomes progressively important with increasing ionic strength, whereby their range and frequency increase. The work of adhesion due to bridging is about 0.3 mN/m. At low ionic strengths, the films behave differently. While the highly charged PVA shows unspecific adhesion at small distances, the more weakly charged PVA analog shows few adhesion events occurring at long distances.     

Three‐dimensional Arrangement of Short DNA Oligonucleotides at Surfaces via the Synthesis of DNA‐branched Polyacrylamide Brushes by SI‐ATRP

Short DNA oligonucleotide branches are incorporated into acrylamide brushes via surface initiated atom transfer radical polymerization in an attempt to increase DNA surface density by building three‐dimensional molecular architectures. ATR‐FTIR as well as hybridization studies followed by SPR confirm the incorporation of the DNA sequences into the polymer backbone. MALDI‐TOF analysis further suggests that six acrylamide monomer units are typically separating DNA branches present on a single brushes approximately 26 units long. This new approach offers a promising alternative to SAM‐based nucleic acid and aptamer sensors and could enable the realization of more complex soft materials of controlled architecture capable of both recognition and signaling by including additional optically or electrochemically active moieties.

     

A comparison of polymeric materials as pre-concentrating media for use with ATR/FTIR sensing

Polymer-modified ATR-FTIR spectroscopy was investigated to determine its potential suitability for use as an analytical methodology for process stream analysis. The process stream under investigation contains toluene, tetrahydrofuran, ethanol, and acetonitrile in an aqueous matrix. Four polymers, Teflon® AF2400, poly(acrylonitrile-co-butadiene) (PAB), polydimethylsiloxane (PDMS), and poly(styrene-co-butadiene) (PSB), were chosen for study based on partition coefficients measured using a novel automated GC technique. Polymer suitability as pre-concentration media was assessed utilizing analyte/polymer diffusion coefficient data, equilibrium absorbance values, water ingress, and polymer plasticization. PAB displayed the fastest sensing times and enhanced sensitivities. Teflon® AF2400 demonstrated a low water absorption and a low degree of plasticization. Other factors affecting the diffusion rate of analytes were also investigated including molecular size, shape and analyte concentration. This research demonstrated that the choice of pre-concentrating medium is not a trivial issue, being dictated by a combination of sensitivity constraints as well as polymer robustness in real sample matrices.     

Characterising and correcting batch variation in an automated direct infusion mass spectrometry (DIMS) metabolomics workflow

Direct infusion mass spectrometry (DIMS)-based untargeted metabolomics measures many hundreds of metabolites in a single experiment. While every effort is made to reduce within-experiment analytical variation in untargeted metabolomics, unavoidable sources of measurement error are introduced. This is particularly true for large-scale multi-batch experiments, necessitating the development of robust workflows that minimise batch-to-batch variation. Here, we conducted a purpose-designed, eight-batch DIMS metabolomics study using nanoelectrospray (nESI) Fourier transform ion cyclotron resonance mass spectrometric analyses of mammalian heart extracts. First, we characterised the intrinsic analytical variation of this approach to determine whether our existing workflows are fit for purpose when applied to a multi-batch investigation. Batch-to-batch variation was readily observed across the 7-day experiment, both in terms of its absolute measurement using quality control (QC) and biological replicate samples, as well as its adverse impact on our ability to discover significant metabolic information within the data. Subsequently, we developed and implemented a computational workflow that includes total-ion-current filtering, QC-robust spline batch correction and spectral cleaning, and provide conclusive evidence that this workflow reduces analytical variation and increases the proportion of significant peaks. We report an overall analytical precision of 15.9 %, measured as the median relative standard deviation (RSD) for the technical replicates of the biological samples, across eight batches and 7 days of measurements. When compared against the FDA guidelines for biomarker studies, which specify an RSD of <20 % as an acceptable level of precision, we conclude that our new workflows are fit for purpose for large-scale, high-throughput nESI DIMS metabolomics studies.     

Cohomology pairings on singular quotients in geometric invariant theory

In this paper we shall give formulas for the pairings of intersection cohomology classes of complementary dimensions in the intersection cohomology of geometric invariant-theoretic quotients for which semistability is not necessarily the same as stability (although we make some weaker assumptions on the action). We also give formulas for intersection pairings on resolutions of singularities (or more precisely partial resolutions, since orbifold singularities are allowed) of the quotients.     

Decomposing bridging adhesion between polyelectrolyte layers into single molecule contributions

A novel approach to analyze the force response of multiple polymer strands, which are bridged between two surfaces, is proposed. The response of single polymer strands is experimentally accessible by measuring the force upon separation of two polymer-coated surfaces with the atomic force microscope. Our approach is based on the decomposition of the stretching and desorption sequence into contributions of independently bridged chains and of the elimination of loops formed on the opposite surface during contact. This approach was applied to investigate the bridging adhesion of surfaces coated with poly(vinylamine) (PVA). The force response of single PVA molecules was described on the basis of a recently proposed model, which accounts for the discrete chain character of the polymer at higher extension forces. As exemplary results, we determined the length distributions of the individual chains and the loop number distribution of these bridging chains on the polyelectrolyte-coated surfaces. The former were compared with scaling theories of polymer adsorption.